Glucose Metabolic Alterations in Isolated and Perfused Rat Hepatocytes Induced by Pancreatic Cancer Conditioned Medium: A Low Molecular Weight Factor Possibly Involved

• Published in: Biochemical and biophysical research communications 1999-04, Vol.257 (2), p.622-628
• Main Authors: Valerio, A., Basso, D., Brigato, L., Ceolotto, G., Baldo, G., Tiengo, A., Plebani, M.
• Format: Article
• Language: English
• Subjects: 1,2-diacylglycerol; Animals; Biological Factors - metabolism; Biological Factors - pharmacology; Cell Membrane - metabolism; Cells, Cultured; Culture Media, Conditioned - metabolism; Culture Media, Conditioned - pharmacology; Cytosol - metabolism; Diglycerides - metabolism; Epidermal Growth Factor - pharmacology; Glucose - metabolism; growth factors; Humans; Insulin Resistance; Interleukins - pharmacology; Lactic Acid - metabolism; Liver - cytology; Liver - drug effects; Liver - metabolism; Male; MIA PaCa2 tumor cells; Molecular Weight; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - metabolism; Perfusion; Protein Kinase C - metabolism; protein kinase-C; rat hepathocytes; Rats; Rats, Wistar; Transforming Growth Factor beta - pharmacology; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0521

A serious insulin resistance characterizes pancreatic cancer-associated diabetes mellitus. Elsewhere, we demonstrated that MIA PaCa2 cultured cells secrete a soluble factor responsible for reduced glucose tolerance induced in SCID mice. The intracellular mechanism of insulin resistance was investigated in isolated and perfused rat hepatocytes incubated with MIA PaCa2 conditioned medium. Lactate production was reduced compared to hepatocytes incubated with control medium while 1,2-DAG was increased and PKC was activated in the hepatocytes incubated with MIA PaCa2 conditioned medium. This behavior was not reproduced treating the hepatocytes with the growth factors EGF, interleukin Iβ, interleukin-6, and TGF-β1. In an attempt to make a biochemical identification of the hypothesized tumor associated-diabetogenic factors we observed a low molecular weight protein in the conditioned medium, absent in the nonconditioned one, that may be responsible for the described behaviors.